Risk factors for cerebrovascular disease, such as hypertension, obesity, and diabetes, rarely occur in isolation. The clustering of three or more vascular risk factors comprises a clinical diagnosis of cardio-metabolic syndrome (CMS). In recent years, the prevalence of CMS has risen dramatically, with recent estimates of nearly 34% of US adults meeting criteria. A diagnosis of CMS in midlife, even prior to the development of clinically significant neurologic symptoms, is associated with a substantially increased risk for vascular-related neurodegenerative conditions, including vascular cognitive impairment, dementia, as well as major neurologic events such as stroke. While there is a great deal of research examining the negative impact of individual factors, such as blood pressure, on brain tissue, there is still little knowledge of the neural mechanisms underlying CMS-related changes to neural health. The current project seeks to better understand how multiple co-occurring risk factors affect vascular and neural integrity, and how cognitive and functional status is subsequently impacted. We will identify noninvasive neuroimaging, cognitive and functional biomarkers of CMS that can be used in detecting who may be at greater risk for cognitive decline and dementia. This will be accomplished with three Aims that include 1) understanding how CMS impacts specific structural and functional brain networks, 2) understanding how an index of vascular integrity, cerebrovascular reserve (CVR), impacts structural and functional brain networks in CMS, and 3) understanding how CVR interacts with structural and functional brain integrity to affect cognitive, psychiatric, and functional status. Ultimately, this project ams to provide important translational data that can be used in clinical settings for the treatment and management of multiple vascular risk factors.